Epigenetic inactivation of 14-3-3 sigma in oral carcinoma: association with p16(INK4a) silencing and human papillomavirus negativity.
Cancer Res
; 62(7): 2072-6, 2002 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-11929827
ABSTRACT
In vitro studies have identified 14-3-3sigma as a regulator of senescence in human keratinocytes. To assess its contribution to squamous neoplasia, we have analyzed genetic and epigenetic changes in this gene in squamous cell carcinomas (SCCs) and dysplastic lesions of the oral cavity. No mutations were detected in the coding sequence of 14-3-3sigma in 20 oral carcinomas, and there was loss of heterozygosity in only 7 of 40 informative cases. In contrast to the absence of genetic change, aberrant methylation within 14-3-3sigma was detected in 32 of 92 squamous cell carcinomas and in 3 of 6 oral dysplasias and was associated with reduced or absent expression at both mRNA and protein levels. Methylation was not detected in matched, normal epithelial tissue controls. Carcinomas in which 14-3-3sigma was methylated were significantly more likely to lack DNA sequences from human papillomavirus and to have coincident methylation of p16(INK4a) than cases that expressed 14-3-3sigma. Methylation was detected in SCC, both wild-type and mutant for p53, but was more commonly detected in cancers with wild-type p53. These results implicate coincident epigenetic abrogation of function in both sigma and p16(INK4a) in a subset of SCCs of the oral cavity.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Papillomaviridae
/
Lesiones Precancerosas
/
Neoplasias de la Boca
/
Carcinoma de Células Escamosas
/
Proteínas
/
Biomarcadores de Tumor
/
Inhibidor p16 de la Quinasa Dependiente de Ciclina
/
Exonucleasas
/
Proteínas de Neoplasias
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2002
Tipo del documento:
Article
País de afiliación:
Italia